beta-erythroidine and its hydrohalides, and a process for their production



Patented Apr. 17, 1945 e-ERYTHROIDINE. AND ITS; HYDROHALIDE-S, ,AND A PROCESS FOR THEIRPRODUCTION' 'Karl Folkers, Plainfield, and Randolph T. Major,

- Mountainside, N. J., assignors to Merck & 00.,

Inc., Rahway, N. J a corporation of New Jersey 7 No Drawing Application November 13,1942,-.

H Serial No. r I 8 Claims. (01. 260- 236) This invention relates to a physiologically ac I I tivej alkaloid, and to processes for its production.

The'alkaloid of the present invention exhibits a potent curare-like action, and has been found to be particularly useful-for the release of spasm psychoses.

roidine.

a mixture of stereoisomers.

dine.

ying.

stance.

with appropriate reagents:

e-Erythroidine hydrochloride.hemihydratej M. P.

2295-230 0. (decompo. I v c Erythroidinehydrochloride, anhydrous; M. P. 232 C, (decomp.), [d1 =+iO9.0,- water.

p-Erythroidine hydrobromide' containing, oneand plastic muscular rigidity in patients afflicted half molecule of. ethanol; M. P422790. with spastic paralysis, "and for modification of p-Erythroidine hydrobromide, anhydrous; M. P. the severity of meti'azol convulsions, thereby pre- 222.5 C.; (a) =+1l1.2, water. venting fracture in the convulsive therapy of the p-Erythroidine hydriod-ide, anhydrous; M. P. 206

It is being used with notable success C.; (d) =+108.1, water. in the field of shock therapy? p-Erythroidine perchlorate; M. P. 203-2035 C; In a co-pending application, Serial No. 391,096, Watere filed April 30, 1941, we have described a new er t r idi e flav a ate; 216-2165" Erythrma alkalmdwblch We have calldferytht Alkali and alkaline earth metal salts of the P has the f m acid corresponding to the lactone, c erythroidine, m C16H19NO3, 1S lactone whlch 1s suscep' may be obtained by treating said c-erythroidine tible to destruction by strong alkali, forms a in aqueous Solution with an appropriate, a1ka crystalline hydrochloride melting at about linizing agent as, for example, sodium hydroxide. usually m the range of 223-2320 and 1s This application is a continuation in-part of our application Serial No, 233,412, filed October The present application is more particularly 5 1933. concerned with one of the stereoisomers of Modifications may be made in carrying out the erythmldme, t W have t present invention, without departing from the F'Erythmldme 1s i Substance spirit and scope thereof, and we areto be limitwh ch is a lactone and which, in its substantially ed only by the appended Claims page forri,]li igs a melting t(point of about 99.5- claim. 1 O a D 1 The process for the production of b -er th- Accolidmg to 9 y roidine which in its substantially puge f or m be obtained by crystallization, preferably repetihas a melting point of about ,99 5 100o tive, of a salt or hydrohalide of the stereoisomeric (a) 25: +83 8 Water and which a mixture erythruidine from a Solvent Such as isorger of n igth fi u Said u yt u ethanol or methanol d preferably absolute ing an alkaloidal substance of formula'CwI-IwNOs, ethaml 9 methaml- P i and identical with the alkaloid erythroidine hYdrha1,1d-e of ls'erythroldme 15 thus 'P obtained from Erythrina amerz'cana, comprising In Instances, sucfh saltor hyrohahde may crystallizing a substance selected from the group be obiialned as hemlhydmte, y- 3 consisting of acid salts and hydrohalides of comphshed by alcohol of crystallization, in which erythroidinen fr m a Solvent selected r case the anhydrous form may be Obtained by group consisting of ethanol and methanol, and

0 recovering p-erythroidine. t The base, fld may be recovered 2. The process for the production of p-erythfrom such salt or hydrohalide by dissolving the Toidim; which in its Substantially pure form latter in water, rendering the solution weakly has melting point of b t; 99540 alkaline, as for example by the addition thereto =+88 8, water, and which is a stereoof sodium bicarbonate, and exhaustively e tr isomer of erythroidine, said erythroidine being with a solvent such as ch orofo for ing an alkaloidal substance of formula C16Hi9NO3,

and identical with the alkaloid erythroidiiie- It is, of course, possible to u il e the base 1 obtained from Erythrina amer'z'ccma, comprising erythroidine as a i material for the repeatedly crystallizing a substance selected from .tion of a wide variety of derivatives. The folthe group consisting of acid salts and hydr owi derivatives are illustrative of those w i halides of erythroidine from a solvent selected ay b pr e ei er y trea n the correfrom the group consisting of ethanol and methasponding derivative of erythroidine as de- 1101, d recovering p erythroidine scribed, or by reacting the base, c-erythroidine, 3. The process for the production of p-eryth roidine which in its substantially pure form.

has a melting point of about 995-100 C.; (u) =+88.8,' water, and which is a stereoisomer of erythroidine, said erythroidine being an alkaloidal substance of formula C16H19NO3, and identical with the alkaloid erythroidine obtained from Erythrina amencana, comprising crystallizing the hydrochloride of erythroidine from a solvent selected from the group consisting of ethanol and methanol, and recovering p-erythroidine.

4. The process for the production of c-erythroidine which in its substantially pure form has a melting point of about 995-100" 0.; (a) =+88.8, water, and which is a stereoisomer of erythroidine, said erythroidine being an alkaloidal substance of formula (lisl-lisNOs, and identical with the alkaloid erythroidine obtained from Erythrina americana, comprising repeatedly crystallizing the hydrochloride of "erythroidine from a solvent selected from the group consisting of ethanol and methanol, and recovering fl-erythroidine.

5. A product selected from the group consisting of p-erythroidine an alkaloidal substance of formula C16H19NO3, which in its substantially pure form has a melting point of about 99.5-100 0.; (a) =-|-88.8 water, and which is identical with the fi-erythroidine obtained from species of Erythrina; and salts and hydrohalides of said p-erythroidine.

6. The hydrochloride of fi-erythroidine, which p-erythroidineis an alkaloidal substance of formula C16H19NO3 which, in its substantially pure form has a melting point of about 995-100 C.; (a) =+88.8, water, and which is identical with the p-erythroidine obtained from species of Erythrina. I

'7. The hydrobromide of c-erythroidine, which p-erythroidine is an alkaloidal substance of formula Ciel-119N03 which, in its substantially pure form has a melting point of about 99.5-100 C.; (a) =+88.8, water, and which is identical with the B-erythroidine obtained from species of Erythrina.

8. As a new product, p-erythroidine, which in tained from species of Erythrina.

KARL FOLKERS. RANDOLPH T. MAJOR. 

